Oral tetracyclines (tetracycline, doxycycline, minocycline and lymecycline) have been commonly regarded as effective for treating both inflammatory and non-inflammatory acne. An excellent review of efficacy of 57 clinical trials by Simonart et al. in 2007 concluded that compared to the baseline before treatment, efficacies of all tetracyclines were similar (mean reduction in inflammatory lesions and non-inflammatory lesion being 54.3 ± 1.4% and 45 ± 2.6%, respectively) and were not affected by dosage amount (40 - 1,000 mg per day) and treatment period (4 - 24 weeks). These interesting findings may be pharmacodynamically rationalized by weak intrinsic anti-acne activity of tetracyclines and strong placebo effects. This hypothesis was supported by published data indicating that during weeks or months of daily administration, the placebo effect approached the effect of minocycline or doxycline in reducing acne lesions in three separate studies. The present work suggests the importance of considering placebo effects in the evaluation of anti-acne products. The treatability of acne was discussed in view of the slow and weak intrinsic anti-acne property of oral tetracyclines, and the reported fast (within days) elimination (curing) of severe acne by intralesional corticosteroids and antibiotics. The subantimicrobial or non-antimicrobial doses (e.g., only a small fraction) of various oral tetracyclines may be much lower than those commonly recognized.