Excess fluoride (F − ) inhibits the growth and metabolism of several crop plants, while some have an innate ability for F − tolerance. The present study was undertaken to explain how plants tolerate F − toxicity and understand the efficacy of exogenous stress protectants and phytoremediation approaches for F − homeostasis and tolerance of crop plants. This review comprehends existing information available so far on the F − accumulation toxicity and tolerance mechanisms. A high level of F − inhibits plant growth, water and nutrition uptake, enzyme activity, and yield. This review concludes that plants tolerate through F − homeostasis (exclusion, chelating, and compartmentalization) and gene activation for enhanced pathways of antioxidants, hormones, osmolytes, stress proteins, transporters, and metabolites. Exogenously applied stress protectants like salicylic acid (SA), polyamines (PAs), melatonin (Mel), glycine betaine, calcium (Ca 2+ ), and nanoparticles are differentially effective in reducing F − accumulation and toxicity by regulating various pathways. Application of minerals minimizes the F − accumulation through changing pH of soil, chelate formation with F − , and permeability of the cell membrane. Although many of the physiological aspects (enzyme activities, F − accumulation and regulation) were studied earlier, however, an effort has been made for the first time to understand the genetic basis and role of stress protectants and mineral nutrition, regulating these physiological activities, and explore new integrated approaches related to F − mitigation by means of phytoremediation. This review covers the recent development in F − transporters, gene expression, and biochemical and hormonal levels which could be utilized in regulating F − toxicity through omics and transgenic approaches in the future.