The Cure Huntington's Disease Initiative's (CHDI) Fifth Annual HD Therapeutics Conference provided a forum for translational researchers and clinicians to discuss approaches to improve drug discovery and development for Huntington's disease (HD). Presenters were primarily from academia, but the conference also had notable representation from the pharmaceutical and industrial research sectors. The conference program focused on developing and understanding disease biomarkers to inform preclinical and clinical research, in vivo models of HD, huntingtin (Htt) protein function, and research on drugs under development for HD. Exciting highlights of the conference included a proposal to use network-based approaches to understand HD and to identify therapeutic targets, the potential for sheep as a viable large animal model, the advent of a'phenocube', discussions on antisense technology and allele-selective depletion of the mutant Htt protein, and reports of drugs for HD that may soon enter the market.