The therapeutic options in the treatment of cancer therapy have been recently significantly increased with systemic immune-targeted therapies. Novel immunotherapy approaches based on immune checkpoint blockade or engineered cytotoxic T lymphocytes have reached late-stage clinical development, with highly encouraging results. The success of cancer immunotherapy has generated a tremendous interest in further developing and exploring these strategies in combination with other approaches such as radiotherapy and local ablative therapies in oncology. The goal of this review is to discuss current approaches in immunotherapy and provide simple and constructive explanations on their mechanisms of action as well as certain more common and serious toxicities.