Natural organic matter (NOM) plays key environmental roles in both aquatic and soil systems. A long-standing approach for evaluating NOM composition and activity is to extract soils with alkali solutions to obtain humic substances, namely humic acids (HA), and fulvic acids (FA), or to briefly expose isolated fractions of dissolved organic matter to alkali. Critics have claimed these methods create laboratory artifacts and are thus unsuitable for studying NOM behavior in field conditions. In response, we describe case studies in which humic fractions were analyzed to identify significant processes in environmental or agricultural issues. Specifically, humic fractions played a key role in maintaining toxic levels of arsenic (As) in drinking water supplies in South and Southeast Asia. Elsewhere, binding reactions of FA and HA with prions were shown to provide a plausible mechanism for variable persistence of prion infectivity across soil types. Humic substances were also shown to enhance iron (Fe) uptake by plants in solution culture and field conditions. Their specific binding sites for mercury (Hg) as determined in laboratory conditions enabled accurate modeling of soil Hg binding under varying conditions. A young HA fraction reproduced in controlled conditions the capacity of animal manure to maintain potassium (K) availability in strongly K-fixing field soils, leading to development of a commercially successful humic-K fertilizer. Humic fractions accurately represented NOM across multiple settings and research objectives while providing novel opportunities for advanced analyses. The study of humic fractions has helped resolve scientific and practical issues in aquatic and soil systems. © 2019 The Author(s).