Natural Product Antifoulants (NPAs) have been proposed as one of the best replacement options for the most successful antifouling agent, tri-n-butyl tin (TBT), which, due to its ecological incompatibility, is currently facing total global ban imposed by International Maritime Organization (IMO). Realizing the importance, commercial and industrial, of immediately finding a suitable replacement for TBT, the research on NPAs has gathered considerable momentum during the last two decades, as evidenced from the sudden spurt in the number of publications and the number of NPAs being reported. Although commendable effort has been expended, more challenges remain ahead before realizing their applications at an industrial scale.