Primary immunodeficiencies are a diverse group of disorders characterised by impaired immune function, often presenting with recurrent infections, autoimmune manifestations or malignancies. Delayed or missed diagnosis is a frequent pitfall due to the variability in presentation and overlap with other conditions. Clinicians must maintain a high index of suspicion, particularly in patients with recurrent or unusual infections, autoimmune cytopenias or failure to thrive, and pursue targeted immune testing and early referral to a rheumatologist. Basic laboratory tests, such as full blood count and immunoglobulin levels, can miss subtle immunodeficiencies. Specialised testing, including functional assays and genetic analysis, is often necessary. Non-infectious manifestations like autoimmune diseases or early-onset malignancies are common and should prompt consideration of primary immunodeficiencies. Immunosuppressive therapies require cautious use, as excessive immunosuppression can exacerbate infections. Immunoglobulin replacement therapy is a cornerstone for managing antibody deficiencies, and early initiation can prevent complications. Long-term monitoring is essential to manage infections, malignancies and organ damage, optimising outcomes and improving the quality of life for patients with primary immunodeficiencies.