CD8(+) T cells (also called cytotoxic T lymphocytes) play a major role in protective immunity against many infectious pathogens and can eradicate malignant cells. The path from naive precursor to effector and memory CD8(+) T-cell development begins with interactions between matured antigen-bearing dendritic cells (DCs) and antigen-specific naive T-cell clonal precursors. By integrating differences in antigenic, costimulatory, and inflammatory signals, a developmental program is established that governs many key parameters associated with the ensuing response, including the extent and magnitude of clonal expansion, the functional capacities of the effector cells, and the size of the memory pool that survives after the contraction phase. In this review, we discuss the multitude of signals that drive effector and memory CD8(+) T-cell differentiation and how the differences in the nature of these signals contribute to the diversity of CD8(+) T-cell responses.