Naturally durable wood pre-dates preservative-treated wood and has been demonstrated to offer a suitable service life for certain applications where preservative-treated wood is not feasible. Heartwood extractives have been demonstrated to impart bio-deteriorative resistance to naturally durable wood species. These extractives are typically found in the heartwood of living trees and are produced either by the death of parenchyma cells or as the result of external stimuli. The mechanisms of natural durability are not well understood, as heartwood extractives can be extremely variable in their distribution, composition, and efficacy in both living and harvested trees. The underlying complexity of heartwood extractives has hindered their standardization in residential building codes for use as wood preservatives. The use of naturally durable lumber is not always feasible, as woods with exceptionally durable heartwood do not typically yield lumber with acceptable machining properties. A potential approach to overcome the inherent difficulty in establishing guidelines for the appropriate use of naturally durable wood is to focus solely on the extractives as a source of bioactive protectants based on the strategies used on living and dead wood to repel the agents of biodeterioration. This critical review summarizes the relevant literature on naturally durable woods, their extractives, and their potential use as bio-inspired wood protectants. An additional discussion will be aimed at underscoring the past difficulties in adopting this approach and how to overcome the future hurdles.