End-stage renal disease is growing in prevalence and incidence. With technical advancements, patients are living longer on hemodialysis. Depression is the most prevalent comorbid psychiatric condition, estimated at about 25% of end-stage renal disease samples. The identification and assessment of depression are confounded by the overlap between depression symptomatology and uremia. Several recent studies have employed time-varying models and identified a significant association between depression and mortality. Due to the high prevalence of depression and the potential impact on survival, well-constructed investigations are warranted.