Osteonecrosis of the femoral head (ONFH) is a disabling disease affecting young adults, which usually leads to the destruction of the hip joint. It is mainly due to an inadequate blood supply that causes the death of osteocytes and bone marrow cells. Joint salvaging procedures are numerous but relatively inefficient, justifying the need for new therapeutic strategies. In this regard, the recently discovered interleukin (IL)-33 alarmin appears as a possible target. Indeed, IL-33 seems to be specifically released by necrotic cells, and interestingly, is constitutively expressed in human bone, in particular by osteocytes, osteoblasts and marrow adipocytes. Moreover, recent reports suggesting that IL-33 modulates angiogenesis, vascular permeability, osteoclastogenesis and bone resorption, indicate that IL-33 may play a role in ONFH.