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Immunotherapy for cancer has fundamentally changed the way we are treating patients with metastatic disease. The exploding interest in immunotherapy has been propelled by the rapid and durable responses seen in treated patients, often with little to no side effects. Billions of dollars are now being poured into immunotherapy research with multiple new approvals since 2010 and even more expected in the near future. However, the basics of immunotherapy, taught in medical schools when our current generation of medical oncologists trained, are inadequate for the high-tech immunotherapies being tested with ever-increasing intensity. In addition, the side effect profile with immunotherapies is related to the mechanism of action and is unique among anti-cancer agents. The mechanism of action is more complex as often agents don’t directly target the cancer but rather target the immune system which, in turn, targets the cancer. Furthermore, the kinetics of a clinical response following immunotherapy may be different from conventional therapy which is important for practitioners and patients alike to know to help manage expectations. Finally, the mechanisms of resistance to immunotherapy are also unique and a better understanding of these mechanisms will guide combination therapy.