The successful derivation of human induced pluripotent stem cells (hiPSCs) by 
dedifferentiation of somatic cells offers significant potential to overcome 
obstacles in the field of cardiovascular disease. hiPSC derivatives offer 
incredible potential for new disease models and regenerative medicine therapies. 
However, many questions remain regarding the optimal starting materials and 
methods to enable safe, efficient derivation of hiPSCs suitable for clinical 
applications. Initial reprogramming experiments were carried out using 
lentiviral or retroviral gene delivery methods. More recently, various nonviral 
methods that avoid permanent and random transgene insertion have emerged as 
alternatives. These include transient DNA transfection using plasmids or 
minicircles, protein transduction, or RNA transfection. In addition, several 
small molecules have been found to significantly augment hiPSC derivation 
efficiency, allowing the use of a fewer number of genes during pluripotency 
induction. We review these various methods for the derivation of hiPSCs, 
focusing on their ultimate clinical applicability, with an emphasis on their 
potential for use as cardiovascular therapies and disease-modeling platforms.