Controlled clinical trials that evaluate the benefits of adjunctive subantimicrobialdose doxycycline (SDD) with conventional therapy were selected for review. It was deemed important to distinguish between statistically significant and clinically relevant results related to SDD use to help guide clinicians in selecting appropriate therapies. Several investigations demonstrated that SDD prescribed as an adjunct to conventional therapy provides a statistically significant improvement with respect to probing depth reduction, gain of clinical attachment, decreased bleeding on probing, and reduced incidence of disease progression in patients with chronic periodontitis. However, conflicting data were also noted in some studies. Furthermore, it is suggested that the clinical relevance of improvements obtained with SDD beyond those obtained with conventional therapy is debatable. Therefore, clinicians should interpret the data cautiously and differentiate between statistically significant and clinically relevant findings before altering treatment regimens.