Objectives: To evaluate the safety and feasibility of physical rehabilitation and active mobilization in patients requiring continuous renal replacement therapy in the ICU. Data Sources: Medline, CINAHL, PubMed, Pedro, and Cochrane Library were used to extract articles focused on physical activity and mobility in this population. Study Selection: Research articles were included in this review if 1) included adult patients greater than or equal to 18 years old requiring continuous renal replacement therapy located in the ICU; 2) described physical rehabilitation, active mobilization, or physical activity deliverables; 3) reported data on patient safety and/or feasibility. The primary outcome was safety, defined as number of adverse events per total number of sessions. Data Extraction: Five-hundred seven articles were evaluated based on title and abstract with reviewers selecting 46 to assess by full text. Fifteen observational studies were included for final analysis with seven studies focused solely on physical activity in patients requiring continuous renal replacement therapy. Data Synthesis: Four-hundred thirty-seven adult ICU patients requiring continuous renal replacement therapy participated in some form of physical rehabilitation, physical activity, or active mobilization. Two major adverse events (hypotension event requiring vasopressor and continuous renal replacement therapy tube disconnection, pooled occurrence rate 0.24%) and 13 minor adverse events (pooled occurrence rate 1.55%) were reported during a total of 840 individual mobility or activity sessions. Intervention fidelity was limited by a low prevalence of higher mobility with only 15.5% of incidences occurring at or above level 5 of ICU Mobility Scale (transfer to chair, marching in place or ambulation away from bed, 122/715 reports). Feasibility in the provision of these interventions and/or continuous renal replacement therapy-specific deliverables was inconsistently reported. Conclusions: Early rehabilitation and mobilization, specifically activity in and near the hospital bed, appears safe and mostly feasible in ICU patients requiring continuous renal replacement therapy. A cautious interpretation of these data is necessary due to limited aggregate quality of included studies, heterogeneous reporting, and overall low achieved levels of mobility potentially precluding the occurrence or detection of adverse events.