New once-daily formulations of tramadol have been recently marketed in various countries. This review focuses on the matrix systems used in sustained-release formulations to control drug delivery, the pharmacokinetics and pharmacodynamic profile and the available clinical trials on once-daily tramadol. Four controlled clinical studies with a limited number of patients have shown that once-daily tramadol is safe and effective for up to 12 weeks in rheumatological pain treatment, with a favourable side effects profile. Once-daily tramadol has established efficacy superior to that of placebo for pain management and functional improvement in patients with osteoarthritis. Two randomised clinical trials demonstrated similar rates of efficacy between immediate-release and once-daily sustained-release formulation, without significant differences in the use of escape medications and the number of nights woken. Once-daily tramadol offers the advantage of a reduced dosing regimen that improves patient compliance.