Friction blisters are a common sequela of many athletic activities. Their significance can range from minor annoyance to major performance disruptions. The latter is particularly true in baseball pitchers, who sustain repeated trauma between the baseball seams and the fingers of the pitching hand, predominately at the tips of the index and long fingers. Since 2010, 6 Major League Baseball (MLB) players accounted for 7 stints on the disabled list (DL) due to blisters. These injuries resulted in a total of 151 days spent on the DL. Since 2012, 8 minor league players spent time on the DL due to blisters. Moreover, there have been several documented and publicized instances of professional baseball pitchers suffering blisters that did not require placement on the DL but did result in injury time and missed starts. The purpose of this article is to review the etiology and pathophysiology of friction blisters with particular reference to baseball pitchers; provide an overview of past and current prevention methods; and discuss our experience in treating friction blisters in MLB pitchers.