OBJECTIVE: To provide a systematic review of the side effects associated with sorafenib, sunitinib, and temsirolimus and to provide an outline of possible preventive or therapeutic measures. METHODS: We performed a PubMed-based systematic review of side effects associated with the three agents and relied on product monographs and prescribing information to provide an outline of treatments aimed at reducing these toxicities. RESULTS: Side effects range from <1% to 72%. Grade 3/4 side effects are less common and range from <1% to 13% for sorafenib, <1% to 16% for sunitinib, and 1% to 20% for temsirolimus. Overall, sunitinib causes the most grade 3/4 side effects and sorafenib causes the fewest grade 3/4 side effects, although head-to-head trials are required to compare safety profiles of all three kinase inhibitors. Virtually all side effects can be managed effectively. CONCLUSION: Prevention, recognition, and prompt management of side effects are of key importance and avoid unnecessary dose reductions, which may undermine treatment efficacy.