Numerous incremental technological improvements have occurred recently in the application of therapeutic retrovirus-mediated gene transfer into hematopoietic stem cells (HSCs). Improved transduction efficiencies are now reaching levels that may correct some inherited or acquired disorders. Novel retroviral vector systems likewise offer the possibility for an expanded portfolio of treatment approaches. Most importantly, however, investigators are now also focusing efforts on post-transduction events to fully impact correction. Here we describe recent advances in the field, with a special emphasis on the role of post-transduction processes, for correction of disorders or treatments that involve HSCs or their progeny.