A survey of newer analgesics in advanced clinical development suggests that cyclooxygenase-2 inhibitors for inflammatory pain, newer 5-hydroxytryptamine 1D (5-HT 1D) agonists for migraine pain, α-2 adrenergics, neuron-specific Ca++or NA+ channel antagonists, drugs that potentiate opioid analgesics or inhibit morphine tolerance development, or implantation of encapsulated living cell systems that release endorphins or other analgesic peptides, may improve analgesic responsiveness and reduce side effects for some patients with acute or chronic pain conditions. Among the more novel anti-inflammatory anti-arthritic drugs with different mechanisms of action than the dominant nonsteroidal anti-inflammatory drugs are the first new cyclooxygenase-2 inhibitors (celecoxib, vioxx) and two drugs that may have combined immunomodulatory and anti-inflammatory actions (pelubiprofen, enbrel). Other anti-inflammatory, anti-arthritic approaches in earlier clinical testing include two leukotriene antagonists, a C5a complement inhibitor, and matrix metalloproteinase inhibitor.This manuscript details the need for new pain relieving drugs, presents their status, and enumerates the drugs in development.The status of new nonsteroidal anti-inflammatory drugs is described with new mechanisms of action and efficacy for acute and chronic pain use.