Non-viral vectors can be loosely grouped as plasmid DNA, liposome-DNA complexes (lipoplexes), and polymer-DNA complexes (polyplexes). Oligonucleotides and their analogues, either alone or in complexes, are also an example of non-viral vector-mediated gene transfer. A substantial number of the human cardiovascular gene therapy protocols are based on plasmid-mediated gene transfer. Although myocardial plasmid-mediated gene transfer is relatively inefficient, it has been the vector system upon which several therapeutic angiogenesis trials have been based. In this setting, transient secretion of angiogenic factors by a modest number of gene-modified cells is sufficient for the desired phenotypic effect. Inefficient gene transfer and transient gene expression would not, however, be effective for other muscle-based cardiac pathophysiologies, the majority of which demand widespread and sustained transgene expression.