Soft wearable and implantable electronic systems have attracted tremendous attention due to their flexibility, conformability, and biocompatibility. Such favorable features are critical for reliably monitoring key biomedical and physiological information (including both biophysical and biochemical signals) and effective treatment and management of specific chronic diseases. Miniaturized, fully integrated self-powered bioelectronic devices that can harvest energy from the human body represent promising and emerging solutions for long-term, intimate, and personalized therapies. In this Perspective, we offer a brief overview of recent advances in wearable/implantable soft electronic devices and their therapeutic applications ranging from drug delivery to tissue regeneration. We also discuss the key opportunities, challenges, and future directions in this important area needed to fulfill the vision of personalized medicine.