As South Africa continues to battle the second wave of SARS-CoV-2 infections, the imminent arrival of vaccines against COVID-19 offers hope. Vaccine roll-out has been accompanied by heightened media coverage that has created both excitement and anxiety, reporting on the shortened timeline of vaccine trials and approvals, as well as the recent series of anaphylaxis cases associated with the two approved mRNA COVID-19 vaccines. Patients with allergic and other immune-based diseases are subgroups especially concerned about vaccine safety and efficacy. This practice guideline offers broad recommendations for COVID-19 vaccination in various subgroups of allergic and immunebased disease, highlighting risk/benefit evaluation, and where and how routine vaccination should be altered.