Complications due to vertebroplasty may be divided into two categories whether or not they are related to polymethylmethacrylate (PMMA) cement leakage from the compressed vertebral body. PMMA leakage is a very frequent occurrence in vertebroplasty is also the main source of complications. Neurological complications are due to cement leakage into the spinal canal and less exceptionally into the intervertebral foramen. The transpedicular needle approach reduces the risk of cement leakage into the foramen. Pulmonary embolism of PMMA may occur when there is a failure to recognize venous migration of cement early during the procedure. Cortical destruction, presence of an epidural soft-tissue mass, highly vascularized lesions, and severe vertebral collapse are factors which increase the rate of complications, which is therefore much higher in metastatic than in osteoporotic vertebral collapse. Prevention of PMMA leakage-related complications is a multifactorial issue including procedure preparation, needle approach and placement, and cement application. The technical refinements which may help reduce the risk of PMMA leakage are reviewed in this article. Experimental data have shown that systemic reactions may occur during vertebroplasty in the absence of cement leakage. These reactions may be partly related to vascular embolism of bone marrow fat. Another controversial issue is a possible increase in the risk of vertebral collapse of adjacent vertebrae following vertebroplasty. Prospective randomized studies are needed to resolve this issue.