The goal of this review was to determine the current treatment and prevention recommendations for Clostridium difficile infections (CDI) and their efficacy. We elucidate new treatment and prevention strategies that are in development, and define populations that are at greatest risk of CDI. New practice guidelines recommend vancomycin or fidaxomicin as first-line treatment for CDI with oral metronidazole only being used in cases of non-severe CDI when vancomycin and fidaxomicin are not available. Metronidazole is recommended in an IV formulation in conjunction with oral vancomycin in fulminant CDI. Recurrent CDI (rCDI) may be treated with vancomycin, fidaxomicin, or fecal microbiota transplant (FMT). Recent studies show fidaxomicin and fecal microbiota transplantation to be the most effective in decreasing the risk of rCDI. Prevention of CDI is primarily through judicious use of antibiotics and strategies aimed at minimizing the spread of C. difficile spores in hospitals. New preventative options are being studied including an oral beta-lactamase that may decrease the risk of developing CDI after beta-lactam use and a potential vaccine against toxins A and B produced by C. difficile. rCDI continues to be a significant problem particularly in older populations. New treatment guidelines may provide increased protection of recurrence as new medications and treatment modalities are more often utilized. Adjunctive treatments currently being studied may provide additional protection against recurrence but prevention against initial (iCDI) is still of great importance.