HIV self-testing (HIVST) provides an at-home option to counter the barriers that patients face with testing performed in health care settings. HIVST has gradually increased in popularity in a time when social media and technology-based solutions are preferred. In this paper, we consider the aspects of self-testing that merit its integration into HIV testing and prevention systems in the United States. Several elements favor self-testing for large-scale implementation, including ease of use, convenience, potential for integration with mobile health (mHealth), and availability for various modes of distribution. HIVST has a demonstrated ability to reach at-risk individuals who otherwise rarely test. The paradigm of self-testing, however, introduces new challenges, including lesser test performance relative to that in health care settings, nonstandard counseling following receipt of test results, and difficulty in providing linkage to care. After discussing the performance of oral fluid versus blood-based HIVST, we review data regarding acceptability of HIVST, offer insights into counseling and linkage to care for HIVST, and provide examples of novel applications of and future research directions for HIVST.