The emergence of drug-resistant and multi-drug resistant Mycobacterium (M) tuberculosis poses a significant threat to global tuberculosis (TB) control strategies. The prospective design of this study will allow the direct study of infection risk, because the population among which the TB cases arise will be identified and monitored over the course of the study. This study design will permit the characterization and comparison of TB strains with differential success in causing new infections. The study will be conducted within a well-established public health TB control program in a region of Peru, where drug-resistant strains already account for about 20 percent of new TB cases. This study protocol will be implemented in collaboration with the 52 Ministry of Health outpatient health centers in 4 districts of Lima, Peru. This will be a prospective cohort study with an enrollment period of 36 consecutive months. Two types of study subjects will be enrolled: patients found to have active TB disease by routine testing (TB index subjects), and the individuals living in the households of these patients (household members). Study participants will include 4,500 subjects with active TB and their approximately 22,500 household members. Ages will range from less than 1-100 years. The tuberculin skin test will be used to diagnose latent TB infection in the household members. This product is used routinely by health center staff in household members who are children in the age group less than1-15 years. In this study protocol, it will also be used in all household members age 16 years and older. Each TB index subject will remain in the study for a minimum of 12 months and a maximum 48 months. Each household member will remain in the study for 12 months. The primary objective of the study is to measure the risk of infection in household members of index cases with drug-resistant TB compared with the risk of infection in household members of subjects with drug-sensitive TB. This refers to household members who are tuberculin-skin-test negative at the beginning of follow-up. Secondary study objectives are: to assess the impact of sociodemographic and clinical confounders and risk modifiers such as age, sex, comorbidity, human immunodeficiency virus (HIV) infection, nutritional status, and Bacille Calmette Guerin (BCG) vaccination on the association between risk of infection and exposure to a drug-resistant or a drug-sensitive strain; to measure associations between specific mutations associated with drug resistance in M tuberculosis and phenotypes including resistance profile, clinical presentations, and transmissibility; to measure the rate of true relapse versus reinfection in drug-resistant and drug-sensitive TB subjects using molecular-epidemiologic methods; and to measure the rate of reversion (to negative) of the tuberculin skin test among household members with a positive tuberculin skin test result. The primary study outcome measure is the relative risk of TB infection (by tuberculin skin test) in household members of subjects who are sick with drug-resistant M tuberculosis strains compared to household members of subjects with drug-sensitive strains. Secondary study outcome measures are the rate of relapse and rate of reinfection among TB subjects treated with routine TB therapy by outpatient health centers; and the rate of reversion (to negative) of the tuberculin skin test among household members with a positive tuberculin skin test result.