Natural killer (NK) cells are innate immune cells that have long been known to be involved in the recognition and lysis of tumor cells. Despite significant gains in our understanding of the mechanisms that regulate NK cell function, the development of successful NK cell-based therapies has not yet been achieved. However, recent advances in our ability to modulate NK receptor signals and the sensitivity of tumor cells to NK cell-mediated lysis have led to a number of clinical trials testing novel methods to enhance NK cytotoxicity against cancer. Here, we present an overview of current therapies.