Cancer is a multistage process that numerous modalities including systemic treatment can treat. About half of the molecules that have been approved in the last few decades count for plant derivatives. This review presents the application of tree/shrub-derived biologically active compounds as anticancer agents. Different parts of trees/shrubs - wood, bark, branches, roots, leaves, needles, fruits, flowers, etc. - contain a wide variety of primary and secondary metabolites that demonstrate anticancer properties. Special attention was paid to phenolics (phenolic acids and polyphenols, including flavonoids and non-flavonoids (tannins, lignans, stilbenes)), essential oils, and their main constituents such as terpenes/terpenoids, phytosterols, alkaloids, and many others. The anticancer properties of these compounds are mainly attributed to their strong antioxidant properties. In vitro experiments on various cancer cell lines revealed a cytotoxic effect of tree-derived extracts. Mechanisms of anticancer action of the extracts are also listed. Examples of drugs that successfully underwent clinical trials with well-established positions in the guidelines created by oncological societies are provided. The review also focuses on directions for the future in the development of anticancer agents derived from trees/shrubs. Applying biologically active compounds derived from trees and shrubs as anticancer agents continuously seems promising in treating systemic cancer.