Immune deficiencies in adults are quite common conditions in medical practice. However, they present with different clinical phenotypes, whether primary or secondary, which makes their diagnosis more tedious, hence diagnostic and management delays. Through this update, we will review the most common immune deficiencies, their presentations and features. This update's main aim was to propose to the practitioner a structured clinical reasoning and approach, in order to suspect an immune deficiency and initiate a guided exploration. It will also be easier for him to know when a referral to the specialist is necessary.