Individuals with kidney failure often elect to undergo kidney transplantation because they believe that they will be more active and return a sense of normality to their lives with a functioning transplant. Therefore it is important to assess whether these objectives are being met. To do so, we can examine health-related quality of life (HRQOL) in transplant recipients. A number of tools have been used for this purpose, including general HRQOL instruments such as the 36-item short-form health survey (SF-36) and transplant-specific surveys such as the Kidney Transplant Questionnaire. In general, HRQOL assessments improve with transplantation in functional and physical domains. However, many factors actually influence HRQOL in a negative way, including comorbid conditions, kidney function per se, rejection episodes and hospitalizations, employment status, and adverse effects of medications. Perceived physical appearance, issues related to sexuality, stress, anxiety, and even guilt complicate the emotional and psychological landscape after transplantation. This constellation of factors may be predictive of posttransplant life events, such as resumption of employment. Posttransplant HRQOL may be exceedingly important in understanding the issues related to adherence with treatment regimens, especially in the pediatric and adolescent transplant populations. HRQOL is now established as an important issue after transplantation. Nonetheless, shortcomings still exist in our ability to address HRQOL after transplantation. In particular, more study of patient-centered interventions is needed. The use of standardized methodologies for patient assessment could improve our ability to identify if such patient-centered interventions actually succeed across populations, and help us further address the panoply of factors encompassed within posttransplant HRQOL.