The leading cause of death in the world, cardiovascular disease (CVD), remains a formidable condition for researchers, clinicians and patients alike. CVD comprises a broad collection of diseases spanning the heart, the vasculature and the blood that runs through and interconnects them. Limitations in CVD therapeutic and diagnostic landscapes have generated excitement for advances in nanomedicine, a field focused on improving patient outcomes through transformative therapies, imaging agents and ex vivo diagnostics. CVD nanomedicines are fundamentally shaped by their intended clinical application, including (1) cardiac or heart-related biomaterials, which can be functionally (for example, mechanically, immunologically, electrically) improved by incorporating nanomaterials; (2) the vasculature, involving systemically injected nanotherapeutics and imaging nanodiagnostics, nano-enabled biomaterials or tissue-nanoengineered solutions; and (3) improving the sensitivity and/or specificity of ex vivo diagnostic devices for patient samples. While immunotherapy has developed into a key pillar of oncology in the past dozen years, CVD immunotherapy and immunoimaging are recently emergent and likely to factor substantially in CVD management in the coming decade. The nanomaterials in CVD-related clinical trials and many promising preclinical strategies indicate that nanomedicine is on the cusp of greatly impacting patients with CVD. Here we review these recent advances, highlighting key clinical opportunities in the rapidly emerging field of CVD nanomedicine.