•Antibody–drug conjugates represent an exciting new class of cancer therapeutics.•ADCs comprise monoclonal antibodies that selectively deliver potent cytotoxic drugs.•Optimization of the antibody, linker and payload of an ADC is critical for success.•Recent ADCs capitalize on new cytotoxins and advances in linker and conjugation methods. Antibody–drug conjugates (ADCs) aim to take advantage of the specificity of monoclonal antibodies (mAbs) to deliver potent cytotoxic drugs selectively to antigen-expressing tumor cells. Despite the simple concept, various parameters must be considered when designing optimal ADCs, such as selection of the appropriate antigen target and conjugation method. Each component of the ADC (the antibody, linker and drug) must also be optimized to fully realize the goal of a targeted therapy with improved efficacy and tolerability. Advancements over the past several decades have led to a new generation of ADCs comprising non-immunogenic mAbs, linkers with balanced stability and highly potent cytotoxic agents. Although challenges remain, recent clinical success has generated intense interest in this therapeutic class. Recent advances in the discovery and development of antibody–drug conjugates have led to FDA approvals and a rich clinical pipeline of promising new cancer therapies.