Multidrug-resistant organisms (MDROs) are an emerging threat in solid organ transplantation (SOT). The changing epidemiology of these MDROs is reviewed along with the growing evidence regarding risk factors and outcomes associated with both colonization and infection in SOT. The management of these infections is complicated by the lack of antimicrobial agents available to treat these infections, and only a handful of new agents, especially for the treatment of MDR GNR infections, are being evaluated in clinical trials. Due to the increased prevalence of MDROs and limited treatment options, as well as organ shortages, transplant candidacy and use of organs from donors with evidence of MDRO colonization and/or infection remain controversial. Increasing collaboration between transplant programs, individual practitioners, infection control programs, and researchers in antimicrobial development will be needed to face this challenge.