The most reliable outcome variable for assessing periodontal regeneration is human histology; however, the morbidity associated with this technique makes it feasible only in isolated case studies designed to prove that a drug, device, or technique is capable of regenerating the lost periodontium including bone, cementum, and functionally oriented periodontal ligament. In the absence of this genuine variable, other "surrogate" variables must be used. Of these, measurement of new bone is the primary alternative. Direct bone measurements, including linear and volumetric assessment, are by far the best tools; however, the need for a second surgical procedure is a definite drawback of this technique. To overcome this problem, other outcomes have been employed: sounding bone measurements is a less invasive method, albeit it is also less accurate. Another tool that has been tested extensively is radiographic analysis. Conventional radiography is not useful in most regenerative trails where minimal or no crestal changes occur. The use of standardized radiographs and image processing techniques to measure alveolar bone changes has not significantly enhanced the applicability of this method. Digital subtraction radiography (DSR) offers some improvement over previous techniques; however, the correlation between the magnitude of clinical bone changes and changes in the digital image is yet to be substantiated. Other variables have been successfully used in regenerative studies. These include clinical attachment level changes, change in probing depth, and gingival recession. The information derived from these variables, especially attachment level changes, supplement and substantiate the direct bone measurements. Other variables that may be monitored are those associated with plaque formation, periodontal pathogens and gingival inflammation; while not direct measures of regeneration, these variables are likely to affect future prognosis and treatment stability. In summary, direct bone measurements are the most ideal surrogate outcome variable, although clinical attachment level measurements are commonly used in large-scale regenerative clinical trials. Clinical response may be assessed at different time intervals; however, the endpoint measurements for regenerative studies should be taken at least 12-months postoperatively.