Pathogenic mycobacteria gain entry to their hosts by inhalation or ingestion where they adhere to different cell types and are subsequently internalized by professional phagocytic cells, such as macrophages or dendritic cells. Multiple pathogen-associated molecular patterns present on the mycobacterial surface are recognized by and interact with a diverse panel of phagocytic pattern recognition receptors, representing the first step of the infection process. This review summarizes the current knowledge on the numerous host cell receptors and their associated mycobacterial ligands or adhesins. It further discusses the downstream molecular and cellular events resulting from the engagement of the various receptor-mediated pathways, leading to either intracellular survival of mycobacteria or to activation of host immune defenses. The content presented herein on adhesins and host receptors may serve as a resource for those developing novel therapeutic approaches, e.g., in the design of anti-adhesin molecules to prevent bacterial attachment and infection. The collection of mycobacterial surface molecules highlighted in this review may also provide potential new therapeutic targets, diagnostic markers, or vaccine candidates to combat these notoriously challenging and persistent pathogens.