Biological
targeting or molecular targeting is the main strategy
in drug development and disease prevention. However, the problem of
“off-targets” cannot be neglected. Naturally derived
drugs are preferred over synthetic compounds in pharmaceutical markets,
and the main goals are high effectiveness, lower cost, and fewer side
effects. Single-target drug binding may be the major cause of failure,
as the pathogenesis of diseases is predominantly multifactorial. Naturally
derived drugs are advantageous because they are expected to have multitarget
effects, but not off-targets, in disease prevention or therapeutic
actions. The capability of phytochemicals to modulate molecular signals
in numerous diseases has been widely discussed. Among them, stilbenoids,
especially resveratrol, have been well-studied, along with their potential
molecular targets, including AMPK, Sirt1, NF-κB, PKC, Nrf2,
and PPARs. The analogues of resveratrol, pterostilbene, and hydroxylated-pterostilbene
may have similar, if not more, potential biological targeting effects
compared with their original counterpart. Furthermore, new targets
that have been discussed in recent studies are reviewed in this paper.