Lyme and other tick-borne diseases are increasing in the United States. Development of tick control tools have focused primarily on the blacklegged tick, Ixodes scapularis Say. Application of acaricides or entomopathogenic fungal agents to kill host-seeking ticks or ticks on rodents can suppress I. scapularis abundance in residential landscapes, but evidence is lacking for impact on human tick bites or tick-borne disease. Similar studies remain limited for the lone star tick, Amblyomma americanum (L.). Other knowledge gaps include how well homeowners and pest control companies perform in the broadcast application of tick-killing products, relative to high efficacy reported in research studies, and the tick-killing potential of natural product formulations exempt from Environmental Protection Agency registration. Area-wide control based on preventing ticks from feeding on their main reproductive host, the white-tailed deer, can suppress populations of both I. scapularis and A. americanum. Some studies also suggest an impact on Lyme disease cases, but this needs to be further validated in larger-scale intervention studies. The effectiveness, scale, cost, and implementation of various tick management strategies are important considerations in efforts to reduce human tick encounters and tick-borne disease. Additional barriers include weak incentives for industry and academia to develop, test, and register new tick and pathogen control technologies, including vaccines targeting humans, tick reproductive hosts, or wildlife pathogen reservoirs. Solutions will need to be ‘two-pronged': improving the tick and pathogen control toolbox and strengthening the public health workforce engaging in tick control at local and state levels.