A method for producing improved enzyme variants, comprising in operable order: a) testing a plurality of singly-substituted enzyme variants in a first test of a first property and a second test of a second property, wherein the property of a parent enzyme is given a value of 1.0 in each test, a favorable first or second property has a value greater than 1.0, and an unduly unfavorable first or second property has a value less than 0.80; b) identifying a substitution in at least one of the singly-substituted enzyme variants that is associated with a favorable first property and which is not associated with an unduly unfavorable second property; c) identifying a substitution in at least one of the singly-substituted protein variants that is associated with a favorable second property and which is not associated with an unduly unfavorable first property; and d) introducing the substitution from step b) and the substitution from step c) into a protein to yield a multiply-substituted enzyme variant; and e) testing the multiply-substituted enzyme variant in the first test and the second test, wherein said multiply-substituted enzyme variant is an improved enzyme variant, and wherein: (i) said parent enzyme is a protease, said first property is stability and said second property is wash performance; or (ii) said parent enzyme is an amylase, said first property is protein expression and said second property is enzymatic activity, and wherein: at least one of the substitutions comprises a net charge change of 0, -1, or -2 relative to the parent enzyme; and at least one of the substitutions comprises a net charge change of +1 or +2 relative to the parent enzyme thereby defining a charge-balanced multiply-substituted enzyme variant; and an improved enzyme variant is a variant which achieves a value of greater than 1.0 in both of said first and second tests, or a value of greater than 1.0 in the first test and a value of 0.80 to 1.0 in the second test. a) testing a plurality of singly-substituted enzyme variants in a first test of a first property and a second test of a second property, wherein the property of a parent enzyme is given a value of 1.0 in each test, a favorable first or second property has a value greater than 1.0, and an unduly unfavorable first or second property has a value less than 0.80; b) identifying a substitution in at least one of the singly-substituted enzyme variants that is associated with a favorable first property and which is not associated with an unduly unfavorable second property; c) identifying a substitution in at least one of the singly-substituted protein variants that is associated with a favorable second property and which is not associated with an unduly unfavorable first property; and d) introducing the substitution from step b) and the substitution from step c) into a protein to yield a multiply-substituted enzyme variant; and e) testing the multiply-substituted enzyme variant in the first test and the second test, wherein said multiply-substituted enzyme variant is an improved enzyme variant, and wherein: (i) said parent enzyme is a protease, said first property is stability and said second property is wash performance; or (ii) said parent enzyme is an amylase, said first property is protein expression and said second property is enzymatic activity, and wherein: at least one of the substitutions comprises a net charge change of 0, -1, or -2 relative to the parent enzyme; and at least one of the substitutions comprises a net charge change of +1 or +2 relative to the parent enzyme thereby defining a charge-balanced multiply-substituted enzyme variant; and an improved enzyme variant is a variant which achieves a value of greater than 1.0 in both of said first and second tests, or a value of greater than 1.0 in the first test and a value of 0.80 to 1.0 in the second test. (i) said parent enzyme is a protease, said first property is stability and said second property is wash performance; or (ii) said parent enzyme is an amylase, said first property is protein expression and said second property is enzymatic activity, at least one of the substitutions comprises a net charge change of 0, -1, or -2 relative to the parent enzyme; and at least one of the substitutions comprises a net charge change of +1 or +2 relative to the parent enzyme thereby defining a charge-balanced multiply-substituted enzyme variant; and an improved enzyme variant is a variant which achieves a value of greater than 1.0 in both of said first and second tests, or a value of greater than 1.0 in the first test and a value of 0.80 to 1.0 in the second test.