Over the years, societies appear to have had a need for stigmatising diseases or persons. Leprosy sufferers were forbidden from becoming priests, as it was thought leprosy was a sexually transmitted disease. Syphilis subsequently replaced leprosy, and in the 1980s, HIV/AIDS became the new target. Infectious diseases generate stigma, especially when they are associated with high mortality or require isolation, as observed with the coronavirus disease (COVID-19) pandemic. Conditions like tuberculosis, HIV/AIDS or mental health disorders carry stigma due to fear, misinformation or cultural beliefs. Stigma manifests as discrimination, isolation or judgement directed towards individuals, which can severely impact their mental, emotional and physical well-being. This in turn affects health-seeking behaviour and health outcomes while contributing to further spread of disease. This chapter discusses stigma in relation to tuberculosis, HIV/AIDS, COVID-19 and mental illness and offers some recommendations through an approach which recognises the need to address empathy and societal structures.