Depressional wetlands in agricultural landscapes are easily degraded by sediments and contaminants accumulated from their watersheds. Several best management practices can reduce transport of sediments into wetlands, including the establishment of vegetative buffers. We summarize the sources, transport dynamics, and effect of sediments, nutrients, and contaminants that threaten wetlands and the current knowledge of design and usefulness of grass buffers for protecting isolated wetlands. Buffer effectiveness is dependent on several factors, including vegetation structure, buffer width, attributes of the surrounding watershed (i.e., area, vegetative cover, slope and topography, soil type and structure, soil moisture, amount of herbicides and pesticides applied), and intensity and duration of rain events. To reduce dissolved contaminants from runoff, the water must infiltrate the soil where microbes or other processes can break down or sequester contaminants. But increasing infiltration also diminishes total water volume entering a wetland, which presents threats to wetland hydrology in semi-arid regions. Buffer effectiveness may be enhanced significantly by implementing other best management practices (e.g., conservation tillage, balancing input with nutrient requirements for livestock and crops, precision application of chemicals) in the surrounding watershed to diminish soil erosion and associated contaminant runoff. Buffers require regular maintenance to remove sediment build-up and replace damaged or over-mature vegetation. Further research is needed to establish guidelines for effective buffer width and structure, and such efforts should entail a coordinated, regional, multi-scale, multidisciplinary approach to evaluate buffer effectiveness and impacts. Direct measures in “real-world” systems and field validations of buffer-effectiveness models are crucial next steps in evaluating how grass buffers will impact the abiotic and biotic variables attributes that characterize small, isolated wetlands.