Natural rubber is a unique biopolymer of strategic importance that, in many of its most significant applications, cannot be replaced by synthetic alternatives. The rubber tree Hevea brasiliensis is the almost exclusive commercial source of natural rubber currently and alternative crops should be developed for several reasons, including: a disease risk to the rubber tree that could potentially decimate current production, a predicted shortage of natural rubber supply, increasing allergic reactions to rubber obtained from the Brazilian rubber tree and a general shift towards renewables. This review summarizes our knowledge of plants that can serve as alternative sources of natural rubber, of rubber biosynthesis and the scientific gaps that must be filled to bring the alternative crops into production.