Treatment of chronic infections requires life-long adherence to medicines. Daily pill fatigue, lack of financial and social support, co-existing conditions, and many other factors can result in failure to adhere to critical life saving medicines. Development of long-lasting controlled release medicines will therefore facilitate a reduction in infectious disease transmission, prevent new infections, improve treatment adherence and limit the emergence of drug resistance and systemic toxicities. Reducing the treatment schedule from daily to monthly or even less-frequent administration of critical treatments could also provide greater patient privacy and satisfaction. It is clear that there remains a greater need for long lasting small molecules against infectious diseases such as viral (e.g. COVID-19, HIV/AIDS and hepatitis infections), bacterial (e.g. tuberculosis and typhoid), and protozoa (e.g. malaria). Given their potential to tackle adherence and reduce the daily drug burden in chronic infections, long-acting formulations of small molecules are in the spotlight of emerging medicines. Our expertise and abilities to transform anti-HIV and anti-Hepatitis B medicines into effective long acting viral reservoir targeted agents will be extended to other conditions such as COVID-19, tuberculosis and malaria. Such long lasting controlled release and effective medicines will provide a paradigm shift in the management of viral, bacterial and protozoa infections in resource limited settings.