In metastatic breast cancer (MBC), interdisciplinary treatment concepts enable longer survival periods with good quality of life. The standard is systemic, biomarker-driven therapy combined with optimal local and supportive treatment. In luminal MBC, endocrine-based therapy with cyclin-dependent kinase (CDK)4/6 inhibitors is given before further endocrine options, targeted therapies, or chemotherapies are used. In triple-negative MBC, immuno-, poly (ADP-ribose) polymerase (PARP) inhibitor, or chemotherapy are used depending on programmed death-ligand 1 (PD-L1) and germline BRCA ([breast cancer gene] gBRCA) status; in second line, the novel antibody-drug conjugate (ADC) sacituzumab govitecan has been established. In HER2-positive MBC, anti-HER2 therapy is administered as a combination of anti-HER2 antibodies with chemotherapy, or in second line and beyond, as an ADC (trastuzumab deruxtecan [T-DXd] or trastuzumab emtansine [T-DM1]) or a tyrosine kinase inhibitor (tucatinib, lapatinib). HER2-low has been gaining importance as a subtype-independent target of T-DXd.