Brucellosis is a reemerging zoonotic infectious disease caused by Brucella spp. and posing significant global health challenges. Focusing on epidemiology, pathophysiology, diagnostic tools, and therapeutic management, the present review synthesizes recent advances in the diagnosis and treatment of brucellosis. Notwithstanding global control efforts, brucellosis remains endemic in various regions, with emerging species and hosts complicating its epidemiology. The mechanisms of Brucella intracellular survival, including evasion of host immune responses and manipulation of cellular processes, contribute to its persistence and pathogenicity. Diagnostic challenges are addressed through culture-based methods, serological tests, and molecular assays, with recent innovations showing enhanced sensitivity and specificity. Treatment involves prolonged antibiotic therapy, consisting in combination regimens tailored to disease severity and patient-specific factors. However, the emergence of antibiotic-resistant strains necessitates continuous surveillance and application of alternative therapeutic strategies. Prevention programs emphasize surveillance and vaccination of livestock, biosecurity measures, and public education designed to reduce transmission. Laboratory safety protocols are crucial to prevent contamination during the handling of suspected brucellosis samples. Future research should focus on proteomic and transcriptomic analyses in view of identifying resistance mechanisms and improving management strategies. This comprehensive review highlights the need for coordinated efforts to control brucellosis and mitigate its impact on public health.