The pathophysiology of hidradenitis suppurativa (HS) is not well understood. Some of our knowledge comes from clinical and epidemiological observations, along with studies of the histopathology and immunohistochemistry of affected skin. More recently, cutaneous molecular studies and transcriptomic analyses have provided additional information regarding inflammatory processes. The chronic cutaneous inflammation, systemic symptoms, and associated comorbidities suggest that HS should be classified as an immune-mediated disease, rather than a primary infectious disease. As such, a proposed integrated disease pathway is presented. At a fundamental level, there appears to be a primary abnormality in the pilosebaceous-apocrine unit, which leads to follicular occlusion, perifollicular cyst development that traps commensal microbes, and rupture into the dermis. This can trigger an exaggerated response of the cutaneous innate immune system. Initially this is an acute event, but ongoing intermittent disease activity can lead to recurrent inflammatory nodules and dermal tunnels. Once underway, the cutaneous inflammation is very difficult to turn off, leading to suppurative inflammation in whole anatomic regions. As the disease progresses, we propose that there is recruitment of the systemic immune system perpetuating the chronic cutaneous inflammatory process. There remains much to be done to understand the pathogenesis and immune signature of this challenging disease.