The coexistence of another diagnosis beside the index disease under study is defined as comorbidity. Comorbidity increases with advancing age. In candidates for radical prostatectomy, two aspects of comorbidity are of interest: its association with perioperative complications and long-term survival. The Charlson score is the most extensively studied comorbidity classification for the prediction of long-term outcome. Several studies have identified this score as an independent prognostic factor in the prostate cancer setting. In addition to the Charlson score, data collected during the preoperative cardiopulmonary risk assessment may deliver information identifying patients with an increased long-term mortality risk. The meaningfulness of comorbidity in predicting overall mortality seems to be comparable to that of the Gleason score, the most important tumor-related predictor of survival in prostate cancer. The identification of prognostically relevant single conditions and the development of a "radical prostatectomy-specific" comorbidity classification might improve the stratification of candidates for radical prostatectomy in the future.