Rice (Oryza sativa L.) is one of the world’s most important crops. However, mankind still faces two major challenges associated with rice, as well as other crops; more rice needs to be produced and better nutritional quality is required. Toxicity of Al³⁺ and Cd²⁺, which is exacerbated by mining and industrial activities, significantly limits rice production. As for FeIII and Zn²⁺, both are essential elements for optimal rice growth. However, they can also limit yield production when present at high concentrations. The importance of these challenges attracted the interest and attention of many laboratories around the world. Consequently, major advances in improving rice tolerance to Al³⁺ and Cd²⁺  toxicity as well as improving FeIII and Zn²⁺ content in the seed, have been made, particularly during the past few years. Advances in Al³⁺ toxicity tolerance are highlighted by the isolation of STAR1&2, two interacting genes that form novel ABC transporter that confers significant Al³⁺ tolerance in rice. As for Cd²⁺, major reduction of Cd²⁺ accumulation in rice grain has been achieved by suppression of the phytochelatin synthase (OsPCS1) gene. For FeIII, substantial reduction of seed phytate content, a strong chelator of FeIII, has been achieved through the repression of the IP3 synthase (RINO1) gene. In addition, ectopic expression of the yeast ferric chelate reductase gene in rice improved rice tolerance to FeIII deficiency. As for Zn²⁺, promising progress has set the stage for bioengineering Zn²⁺ fortified rice endosperm through the overexpression of OsZIP4. Additional advances are also reviewed and presented along with results from our recent work.