The availability of effective antiretroviral therapy has altered HIV from being an acute disease to being a chronic, manageable condition for many people living with HIV (PLWH). Because of their ubiquity and flexibility, mobile phones with short message service (SMS) offer a unique opportunity to enhance treatment and prevention for people managing HIV. To date, very few US studies using SMS for HIV self-management have been published. In this article, we review the published SMS-based intervention research that aimed to improve healthcare quality and outcomes for PLWH and other chronic health conditions, and propose a conceptual model that integrates the communication functionality of SMS with important psychosocial factors that could mediate the impact of SMS on health outcomes. We posit that an SMS-based intervention that incorporates the elements of interactivity, frequency, timing, and tailoring of messages could be implemented to encourage greater medication adherence as well as impact other mutually reinforcing behaviors and factors (e.g., increasing patient involvement and social support, reducing risk behaviors, and promoting general health and well-being) to support better healthcare quality and clinical outcomes for PLWH. We recommend that future studies explore the potential linkages between variations in SMS characteristics and these mediating factors to determine if and how they influence the larger outcomes.