1) The Basics
Overall, I would recommend at least 2 letters from Science Professors, 1 letter from a non-science professor, and two personal letters. By personal I mean from a research PI, a boss, a coordinator, a dean, etc. Not your best friend Timmy! Make sure that you have a doctor letter on hand as one of your personal letters. Other medical staff are great for other letters, but you should ALWAYS send a doctor's letter. You can have more than these five that I recommend, but the minimum requirement that has been highest (to my knowledge) was five letters minimum. Feel free to pick and choose, and to have additional letters for a given school if you know someone with strong ties there (you would send these types of letters directly to them, not with your primary application). If you are applying to a research intense school, a letter from your PI should always be among the letters that you choose to send.
2) Use a letter sending service!
This is sooo much more convenient than having each letter writer send out dozens of letters, or for you to do it for them. The biggest plus of this is that you can bypass some of the "maximum" letter limits, because you only have a single letter packet and schools will accept all of your letters because of this. Whether it makes a difference, I do not know. Regardless, its really convenient because you don't have to worry about things being lost in the mail, as they are sent to schools electronically. You also get confirmations that the service got them, and can select which schools receive them. Many pre-med advising offices do this as a service to their students, check! Otherwise Interfolio is a common one to use.
3) Fresher is better
The ultimate goal of these letters is to evaluate you as you are when you apply, not who you were in your freshman year. Sure, it might be tempting to collect letters from professors early in the game, but it would be much better if you maintained relationships with those professors until your junior year, or alternatively got letters from professors that you were active with in your junior year. This is a much better evaluation of who you are when you apply, and it gives them much more information about your college career to draw upon (discussed in number 5). I know that some of my best experiences came during my late sophomore and early senior year, things that defined me. Furthermore, some of my letter writers had been acquainted with me for years by the time that I asked for letters, and were much more likely to be qualified to evaluate me. Another boon is that, by your junior year, most of your classes will be pretty small. This makes it easier to build relationships with mentors.
4) Fame is nice, familiarity is better
Sure its tempting to get that Nobel laureate to write you a letter of recommendation, but it does you little good if all they write is "Student X went to my class, likes dogs, and asked good questions." This is something that I was told by adcom members that is so often the case. The point of the letters is to evaluate you, not to try and grab as many big names as you can. What good does getting a letter from a professor that knows adcom members if he or she has nothing to say about you, especially if they call him or her up to ask! That being said, one large name might be nice to have, especially if it is someone related to your major, department, or university. The ideal situation is that this person knows you well, and I'd recommend that the "famous guy" be a personal letter than one of your professor letters, just because these are often weighted more heavily (or so I have heard, remember to keep your salt shaker with you!). Bottom line, familiarity is going to get you a better letter. They will be able to talk about you in depth, and give an honest (and hopefully good) estimation of you. This is what you want!
5) Make a info packet for all of your writers!
Even if it's someone that has known you since a child, make sure to type up an extensive summary of who you are (with table of contents). Where you were born, what your parents do, siblings data, high school life and location, college life, jobs, awards, interests, grades, majors, minors, etc. Chances are, most of it won't be very useful to them, but there is always the chance that someone will be able to reference something that you did as part of their estimation, and it allows them to refresh themselves on the details of your life. Basically you want another AMCAS, except feel free to include interests and hobbies (such as traveling) that you didn't! This is why the table of contents is important, so that they don't have to wade through all of it looking for what they want.
6) You must pursue relationships
Want a good letter, you must take the initiative. Even if a professor likes you, chances are they aren't going to show up at your door to hang out. You must put in the time and effort to build connections with your letter writers, it isn't their job. Furthermore, never hesitate to ask someone that you feel might be helpful to be recommended by, for whatever reason. It won't hurt to ask!
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