MCur / Department of Advanced Nursing Science / Survival of children with HIV/AIDS has increased considerably with the use of effective antiretroviral therapy. However, the benefits of this therapy are limited by the difficulty of adherence to the treatment. This study sought to explore the role of professional nurses on anti-retroviral therapy adherence among children in Lejweleputswa district: Free State, South Africa. An exploratory descriptive qualitative research design was used to identify and describe role of professional nurses toward anti-retroviral therapy adherence among children. Population for this study included seventeen (17) professional nurses working in four purposively sampled Primary Health Care clinics invited to participate in the study. Four focus group discussions were conducted in which each group had 6 participants. The transcribed data was analysed using the framework approach of data analysis. Professional nurses in Lejweleputswa district report poor knowledge of parents/caregivers of children, perceived poverty, stigma and discrimination, inappropriate care approaches, and parental dynamics as factors influencing poor ART adherence. Recommendations for enhancing children ART adherence levels in Lejweleputswa district included: mainstreaming adherence counselling in children ART and adopting a comprehensive family centered care approach were identified as measures for improving children ART adherence. Other measures included integration of ART services into Primary Health Care (PHC) services, parental empowerment, development of a programme to reduce stigma and discrimination in the community.