[3] He also served as a Research Fellow at the U.S. Bureau of the Census from 1982 to 1983, an Expert Consultant at the United States Environmental Protection Agency, and a Scientific Associate at the World Fertility Survey.

His doctoral dissertation was on the analysis of data with missing values,[6] and was supervised by Professors Martin Beale and Sir David R. Cox.

After a two-year post-doc in the Department of Statistics at the University of Chicago in 1974-76, Little worked at the World Fertility Survey[7] from 1976–80, under the leadership of Sir Maurice Kendall.

He has participated in many National Academy of the Sciences panels, in particular chairing a studies on multiple sclerosis and other neurologic disorders in veterans of the Persian Gulf and Post 9/11 wars, and on the treatment of missing data in clinical trials.

He has been active in advising the U.S. Food and Drug Administration and pharmaceutical companies on methods for handling missing data in clinical studies[10][11][12][13][14] Little served two terms on the Board of Directors of the American Statistical Association (ASA), first as Editorial Representative and then as a Vice President.

As detailed in that book, initial statistical approaches to missing values were relatively ad-hoc, such as discarding incomplete cases or substituting means.

The main focus of the book is on likelihood-based inferential techniques, such as maximum likelihood and Bayesian inference, based on statistical models for the data and missing-data mechanism.

Little and Rubin defined the field and provided the methodological and applied communities with a useful and usable taxonomy and a set of key results.

[30] Another research area is the analysis of data collected by complex sampling designs involving stratification and clustering of units.