Selective and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) as well as acetaminophen belong to the most widely prescribed therapeutic agents worldwide. Their efficacy in pain relief notwithstanding, the use of NSAIDs is associated with an increased cardiovascular risk, which can be partly attributed to their blood pressure raising potential. Adequately powered placebo-controlled trials specifically evaluating the cardiovascular safety of NSAIDs vs. selective COX inhibitors are currently underway. This review summarizes the current knowledge on the cardiovascular effects of NSAIDs and acetaminophen, and their potential clinical consequences.