An increasing body of evidence indicates that Pycnogenol (PYC), a standardized extract of French maritime pine bark, has favorable pharmacological properties. This is a review of studies with both PYC and components of the preparation, that have helped to elucidate target sites and possible mechanisms for activity in men. Studies appearing in peer reviewed literature, as well as results presented at international meetings not yet available as published papers, are included in this review. Additional data from published sources in German and French languages that are not widely available are also included. Chemical identification studies showed that PYC is primarily composed of procyanidins and phenolic acids. Procyanidins are biopolymers of catechin and epicatechin subunits which are recognized as important constituents in human nutrition. PYC contains a wide variety of procyanidins that range from the monomeric catechin and taxifolin to oligomers with 7 or more flavonoid subunits. The phenolic acids are derivatives of benzoic and cinnamic acids. The ferulic acid and taxifolin components are rapidly absorbed and excreted as glucuronides or sulphates in men, whereas procyanidins are absorbed slowly and metabolized to valerolactones which are excreted as glucuronides. PYC has low acute and chronic toxicity with mild unwanted effects occurring in a small percentage of patients following oral administration. Clinical studies indicate that PYC is effective in the treatment of chronic venous insufficiency and retinal micro-hemorrhages. PYC protects against oxidative stress in several cell systems by doubling the intracellular synthesis of anti-oxidative enzymes and by acting as a potent scavenger of free radicals. Other anti-oxidant effects involve a role in the regeneration and protection of vitamin C and E. Anti-inflammatory activity has been demonstrated in vitro and in vivo in animals. Protection against UV-radiation-induced erythema was found in a clinical study following oral intake of PYC. In asthma patients symptom scores and circulating leukotrienes are reduced and lung function is improved. Immunomodulation has been observed in both animal models as well as in patients with Lupus erythematosus. PYC antagonizes the vasoconstriction caused by epinephrine and norepinephrine by increasing the activity of endothelial nitric oxide synthase. Dilation of the small blood vessels has been observed in patients with cardiovascular disease, whereas in smokers, PYC prevents smoking-induced platelet aggregation and reduces the concentration of thromboxane. The ability to inhibit angiotensin-converting enzyme is associated with a mild antihypertensive effect. PYC relieves premenstrual symptoms, including abdominal pain and this action may be associated with the spasmolytic action of some phenolic acids. An improvement in cognitive function has been observed in controlled animal experiments and these findings support anecdotal reports of improvement in ADHD patients taking PYC supplements. There is much evidence showing that PYC has beneficial effects on physiological functions. Results from ongoing clinical research are required to confirm and extend previous observations.