Sandalwood spike disease (SSD) is likely to be the most destructive of known diseases to infect Indian sandalwood, Santalum album L., which is valued for its wood and scented essential oil derived from the heartwood. Even though the history of research on SSD extends for well over a century, most of the earlier work was primarily descriptive in macromorphological aspects. In 1969, a breakthrough was achieved by three independent research groups that confirmed the causal agent of SSD to be a phytoplasma. Despite this discovery, the identity of the causal agent was only confirmed by a single group using RFLP analysis and nested PCR of 16S rDNA. The phytoplasma that was identified showed high sequence similarity to aster yellows subgroup 16SrI-B. Tissue culture to derive disease-free clones and transgenic strategies to derive disease-resistant trees may be the only realistic solutions for ridding the limited S. album forests of SSD. This brief synthesis aims to stimulate greater interest in SSD, especially since sandalwood production has expanded to the Chinese mainland and to Australia.