Purpose of Review: Aside from absolute indications, the optimal timing of renal replacement therapy (RRT) in critical care is unknown. In this review, we discuss initiation of RRT in relation to both severity of acute kidney injury (AKI) and fluid accumulation. Recent Findings: Results from studies of early vs. late RRT are conflicting, and no definitive conclusions have been made. Observational data points to fluid accumulation as a detrimental factor in critical illness and recent studies have shown that early fluid removal with RRT is feasible and could potentially improve survival. Summary: There is a gap in the knowledge regarding when to initiate RRT in the absence of acute life-threatening complications. Recent studies of fluid accumulation in critically ill patients indicate the importance of avoiding fluid overload, and RRT might play an increasing role in the management of fluid balance in critical care.