This paper presents an updated global QCD analysis of parton distributions in the nucleon, extending the CTEQ series to include new experimental data from the past two years. The analysis incorporates improved experimental data on inclusive jet production and precise deep inelastic scattering (DIS) data, which provide constraints on the gluon distribution over a wide range of $x$. New data on asymmetries in Drell-Yan processes help determine the $d/u$ ratio. The authors discuss various issues in the global QCD analysis, such as the treatment of heavy quark flavors and the interpretation of direct photon production data. They present several sets of new CTEQ5 parton distributions, chosen to meet the needs of different applications, and compare these with results from other recent global analyses. The paper also addresses open problems and uncertainties in the global analysis of parton distributions, emphasizing the importance of quantifying these uncertainties.This paper presents an updated global QCD analysis of parton distributions in the nucleon, extending the CTEQ series to include new experimental data from the past two years. The analysis incorporates improved experimental data on inclusive jet production and precise deep inelastic scattering (DIS) data, which provide constraints on the gluon distribution over a wide range of $x$. New data on asymmetries in Drell-Yan processes help determine the $d/u$ ratio. The authors discuss various issues in the global QCD analysis, such as the treatment of heavy quark flavors and the interpretation of direct photon production data. They present several sets of new CTEQ5 parton distributions, chosen to meet the needs of different applications, and compare these with results from other recent global analyses. The paper also addresses open problems and uncertainties in the global analysis of parton distributions, emphasizing the importance of quantifying these uncertainties.