There is an increasing need to develop high-yielding, disease-resistant crops and reduce fertilizer usage. Combining disease resistance with efficient nutrient assimilation through improved associations with symbiotic microorganisms would help to address this. Arbuscular mycorrhizal fungi (AMF) form symbiotic relationships with most terrestrial plants, resulting in nutritional benefits and the enhancement of stress tolerance and disease resistance. Despite these advantages, arbuscular mycorrhizal (AM) interactions are not normally directly considered in plant breeding. Much of our understanding of the mechanisms of AM symbiosis comes from model plants, which typically exhibit positive growth responses. However, applying this knowledge to crops has not been straightforward. In many crop plants, phosphate uptake and growth responses in AM-colonized plants are variable, with AM plants exhibiting sometimes zero or negative growth responses and lower levels of phosphate acquisition. Host plants must also balance the ability to host AMF with the ability to resist pathogens. Advances in understanding the plant immune system have revealed similarities between pathogen infection and AM colonization that may lead to trade-offs between symbiosis and disease resistance. This review considers the potential trade-offs between AM colonization, agronomic traits and disease resistance and highlights the need for translational research to apply fundamental knowledge to crop improvement.