Treatment adherence to Highly Active Antiretroviral Therapy (HAART) is a critical issue in human immunodeficiency virus (HIV) care. HAART can extend the longevity of people living with HIV, but treatment efficacy relies on strict adherence that is difficult for many consumers to manage. Results presented in this article are based on semi-structured in-depth interviews with Native Hawaiian consumers (n = 6) who reported moderate to low levels of overall HAART adherence, and based on their kokua, or primary support. All interviews were recorded on audiotape, transcribed verbatim, and analyzed using Grounded Theory methods. Research questions that guided the inquiry, included: What are the challenges of Hawaiians who report moderate to low levels of HAART adherence? How does non-adherence occur? What is the role of the kokua (primary caregiver) and/or family members in treatment adherence? What types of support enhance adherence? The unpredictability of living with HIV was a major challenge to adherence. Symptom distress and active use of alcohol and other drugs interfered with the capacity to appropriately adhere. Two patterns of non-adherence were identified: interrupted regime and intermittent use. Tangible and emotional types of support, sometimes delivered in culture-specific ways, were viewed as helpful in maintaining compliance and in resuming the regime when difficulties arose. The findings complement extant research on HAART by providing an understanding of adherence as a lived experience among Native Hawaiians and their kokua.