Bacteria of the genus <i>Legionella</i> are natural pathogens of amoebae that can cause a severe pneumonia in humans called Legionnaires' Disease. Human disease results from inhalation of <i>Legionella</i>-contaminated aerosols and subsequent bacterial replication within alveolar macrophages. <i>Legionella</i> pathogenicity in humans has resulted from extensive co-evolution with diverse genera of amoebae. To replicate intracellularly, <i>Legionella</i> generates a replication-permissive compartment called the <i>Legionella</i>-containing vacuole (LCV) through the concerted action of hundreds of Dot/Icm-translocated effector proteins. In this review, we present a collective overview of <i>Legionella</i> pathogenicity including infection mechanisms, secretion systems, and translocated effector function. We also discuss innate and adaptive immune responses to <i>L. pneumophila</i>, the implications of <i>Legionella</i> genome diversity and future avenues for the field.