T cells are the backbone of adaptive immune responses against various diseases, including cancer. Conventional αβ T cells recognize neoantigens from cancer cells through antigen-presenting cells and generate antigen-specific responses against cancer. They are also quite efficient at generating immunological memory and protecting against the reappearance of the same disease. Despite these strong checkpoints, cancer still progresses via immune escape through different mechanisms. Conventional T cells have been studied for a long time to generate effective therapeutic approaches with variable success rates against many forms of cancer. In addition to conventional αβ T cells, several unconventional T lymphocytes, such as γδ T cells, invariant natural killer T (iNKT) cells, and mucosal-associated invariant T (MAIT) cells, exist in the body and perform widespread and unique functions. γδ T cells can recognize some unique antigens from different metabolic pathways, invariant T-cell receptors (TCRs) on iNKT cells can recognize lipid antigens restricted to the major histocompatibility complex (MHC) I-related molecule CD1d, and MAIT cells can recognize many unique microbial antigens shared by both microbes and cancer cells but not expressed by normal mammalian cells. These cells are also potent effector cells of the immune system that act on cancer cells to various degrees. In this chapter, we highlight the biology, functions, and therapeutic potential of unconventional T cells, such as γδ T cells, iNKT, and MAIT cells, and their importance in the tumor microenvironment and cancer progression.